CHROMATOGRAPHIC RESOLUTION OF CIPROFIBRATE AND INTERACTION OF THE RACEMATE AND BOTH ENANTIOMERS WITH RAT-LIVER MICROSOMES IN-VITRO

The enantiomers of ciprofibrate may be achieved by enantioselective HP LC separation of its methylesters using a OD - Daicel column. Ciprofib rates (racemate and both enantiomers) bind to oxidized cytochrome P-45 0 in rat liver microsomes according type II like aniline or most proba bly as inversed type I, but less pronounced and with a general shift t o the left. Ethylmorphine N-demethylation, ethoxycoumarin and ethoxyre sorufin O-deethylation are all inhibited by the ciprofibrates, most ef fectively ethoxyresorufin O-deethylation by S(-)-ciprofibrate even in mu M concentrations. Microsomal luminol and lucigenin amplified chemil uminescence indicating the formation of reactive oxygen species, micro somal hydrogen peroxide formation and NADPH/Fe stimulated lipid peroxi dation were inhibited in a concentration dependend manner in concentra tion ranges between mM and mu M. This might be due to distinct scaveng er activities of all 3 compounds: the zymosan stimulated chemiluminesc ence of whole blood was completely inhibited in mM concentrations and influenced significantly down to concentrations of 10 mu M, whereas bu rst and phagocytosis tests with human polynuclear leucocytes were not influenced.